BACKGROUND: Colorectal cancer (CRC) remains one of the most common malignancies worldwide, with a significant subset of patients exhibiting absence of carcinoembryonic-antigen (CEA) expression. The lack of effective diagnostic method for CEA-negative CRC prevents its early treatment. AIM: To identify potentially valuable biomarkers for identifying CEA-negative CRC, the hematological characteristics of patients with CEA-negative CRC was investigated. METHODS: In this retrospective analysis, 74 patients were included who had been pathologically confirmed to have CEA-negative CRC, along with 79 individuals diagnosed with benign colorectal conditions. The utility of various biomarkers was evaluated using analysis of the receiver operating characteristic (ROC) curve. RESULTS: Compared with patients with benign colorectal diseases, those with CEA-negative CRC had lower hemoglobin-to-red blood cell distribution width ratio (HRR) and lymphocyte-to-red blood cell distribution width ratio (LRR), and higher platelet-to-lymphocyte ratio (PLR) ( CONCLUSION: HRR, LRR, and PLR alone or in combination could be used to distinguish CEA-negative CRC from benign colorectal diseases.